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Title: | Extracellular haemoglobin upregulates and binds to tissue factor on macrophages: Implications for coagulation and oxidative stress | Authors: | Bahl, Neha Winarsih, Imelda Tucker-Kellogg, Lisa Ding, Jeak Ling |
Keywords: | Science & Technology Life Sciences & Biomedicine Hematology Peripheral Vascular Disease Cardiovascular System & Cardiology Haemolysis lipopolysaccharide sepsis oxidative stress co-evolution of haemoglobin and tissue factor SICKLE-CELL-DISEASE PROCOAGULANT ACTIVITY ENDOTHELIAL-CELLS BACTERIAL-ENDOTOXIN BLOOD-COAGULATION FACTOR EXPRESSION DISULFIDE BOND LIPID-A ACTIVATION LIPOPOLYSACCHARIDE |
Issue Date: | 1-Jan-2014 | Publisher: | GEORG THIEME VERLAG KG | Citation: | Bahl, Neha, Winarsih, Imelda, Tucker-Kellogg, Lisa, Ding, Jeak Ling (2014-01-01). Extracellular haemoglobin upregulates and binds to tissue factor on macrophages: Implications for coagulation and oxidative stress. THROMBOSIS AND HAEMOSTASIS 111 (1) : 67-78. ScholarBank@NUS Repository. | Abstract: | The mechanisms of crosstalk between haemolysis, coagulation and innate immunity are evolutionarily conserved from the invertebrate haemocyanin to the vertebrate haemoglobin (Hb). In vertebrates, extracellular Hb resulting from haemolytic infections binds bacterial lipopolysaccharide (LPS) to unleash the antimicrobial redox activity of Hb. Because bacterial invasion also upregulates tissue factor (TF), the vertebrate coagulation initiator, we asked whether there may be functional interplay between the redox activity of Hb and the procoagulant activity of TF. Using real-time PCR, TF-specific ELISA, flow cytometry and TF activity assay, we found that Hb upregulated the expression of functional TF in macrophages. ELISA, flow cytometry and immunofluorescence microscopy showed binding between Hb and TF, in isolation and in situ. Bioinformatic analysis of Hb and TF protein sequences showed co-evolution across species, suggesting that Hbβ binds TF. Empirically, TF suppressed the LPS-induced activation of Hb redox activity. Furthermore, Hb desensitised TF to the effects of antioxidants like glutathione or serum. This bi-directional regulation between Hb and TF constitutes a novel link between coagulation and innate immunity. In addition, induction of TF by Hb is a potentially central mechanism for haemolysis to trigger coagulation. © Schattauer 2014. | Source Title: | THROMBOSIS AND HAEMOSTASIS | URI: | https://scholarbank.nus.edu.sg/handle/10635/234935 | ISSN: | 0340-6245 2567-689X |
Appears in Collections: | Staff Publications Elements |
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Thrombosis Haemostasis -extracell Hb 2014 (1) 67-78_Ding Lab (.pdf | Published version | 2.14 MB | Adobe PDF | CLOSED | Published |
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